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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02030964




Registration number
NCT02030964
Ethics application status
Date submitted
2/01/2014
Date registered
9/01/2014
Date last updated
9/03/2020

Titles & IDs
Public title
N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan
Scientific title
N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan for Patients With Relapsed or Refractory Neuroblastoma
Secondary ID [1] 0 0
P01CA081403
Secondary ID [2] 0 0
N2012-01
Universal Trial Number (UTN)
Trial acronym
DFMO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuroblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - DFMO
Treatment: Drugs - Celecoxib
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Topotecan

Experimental: DFMO, Celecoxib, Cyclophosphamide & Topotecan - Reconstituted DFMO powder by mouth for 14 days and celecoxib capsule by mouth daily in each cycle. Cyclophosphamide and Topotecan IV on days 8-12 in cycle 1 and days 1-5 of cycles 2-17. Patients may continue for up to 17 cycles as long as therapy is tolerated (no DLT) and disease progression does not occur (SD or better). *Cycle 1 will include a 7 day lead-in with DFMO and celecoxib to deplete tumor polyamines.


Treatment: Drugs: DFMO


Treatment: Drugs: Celecoxib


Treatment: Drugs: Cyclophosphamide


Treatment: Drugs: Topotecan


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events as a measure of safety and tolerability. - The standard 3+3 design for dose escalation will be utilized. 3-6 patients will enroll at each of 4 dose levels, but enrollment to a dosing cohort will cease after observation of DLTs in 2 or more patients. A minimum of 2 to a maximum of 24 patients will be enrolled assuming all 4 dose levels require 6 patients before an MTD is determined. A total of 12 patients may be enrolled at the study defined MTD (including those used to define the MTD) to provide additional adverse event data for safety evaluation.
Timepoint [1] 0 0
Approximately 1 year

Eligibility
Key inclusion criteria
- Patients must be > 2 years and < 30 years of age when registered on study.

- Patients must have recurrent/progressive high-risk neuroblastoma, refractory high-risk
neuroblastoma that had less than a partial response to standard treatment or
persistent high-risk neuroblastoma that had at least a partial response to standard
treatment.

- All patients must have at least ONE site of evaluable disease.

- Patients must have adequate heart, kidney, liver and bone marrow function.

- Patients who have bone marrow disease must still have adequate bone marrow function to
enter the study.

- Patients with other ongoing serious medical issues must be approved by the study chair
prior to registration.
Minimum age
2 Years
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Females of childbearing potential that do not have a negative pregnancy test.

- Patients that are pregnant, breast feeding, or unwilling to use effective
contraception during the study

- Patients status post allogeneic stem cell transplant.

- Patients who, in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study.

- Patients with disease of any major organ system that would compromise their ability to
withstand therapy.

- Patients who are on hemodialysis.

- Patients with an active or uncontrolled infection. Patients on prolonged antifungal
therapy are still eligible if they are culture and biopsy negative in suspected
radiographic lesions and meet other organ function criteria.

- Patients with active bleeding of the GI tract or patients who have symptoms associated
with stomach irritation (known as gastritis).

- Patients who have had a seizure within 12 months prior to enrollment and patients
receiving anti-convulsant therapy for a seizure disorder.

- Patients with known Aspirin-Hypersensitivity triad (asthma, allergic rhinitis, ASA
hypersensitivity).

- Patients with known hypersensitivity to celecoxib or other NSAIDs, aspirin or
sulfonamides.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sydney Childrens Hospital KCC - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Other
Name
New Approaches to Neuroblastoma Therapy Consortium
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will combine an oral drug called DFMO with celecoxib (also oral) and two IV
chemotherapy medicines called cyclophosphamide and topotecan.

- To find the highest dose of DFMO that can be given with celecoxib, cyclophosphamide and
topotecan without causing severe side effects.

- To find out the side effects seen by giving DFMO at different dose levels with
celecoxib, cyclophosphamide and topotecan.

- To measure the levels of DFMO in the blood at different dose levels.

- To determine if your tumor gets smaller after treatment with DFMO, celecoxib,
cyclophosphamide and topotecan.

- To determine if specific gene changes in you or your tumor makes you more prone to side
effects or affects your tumor's response to the combination of DFMO, celecoxib,
cyclophosphamide and topotecan.

- To determine if the amount of normal chemicals in your body called polyamines go down in
response to DFMO, celecoxib, cyclophosphamide and topotecan, and whether you are more
likely to have a good response to the treatment if they do.
Trial website
https://clinicaltrials.gov/show/NCT02030964
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Hogarty, MD
Address 0 0
Children's Hospital of Philadelphia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications